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PARP14 is a PARP with both ADP-ribosyl transferase and hydrolase activities

Đukić, Nina ; Strømland, Øyvind ; Elsborg, Jonas Damgaard ; Munnur, Deeksha ; Zhu, Kang ; Schuller, Marion ; Chatrin, Chatrin ; Kar, Pulak ; Duma, Lena and Suyari, Osamu , et al. (2023) In Science Advances 9(37).
Abstract

PARP14 is a mono-ADP-ribosyl transferase involved in the control of immunity, transcription, and DNA replication stress management. However, little is known about the ADP-ribosylation activity of PARP14, including its substrate specificity or how PARP14-dependent ADP-ribosylation is reversed. We show that PARP14 is a dual-function enzyme with both ADP-ribosyl transferase and hydrolase activity acting on both protein and nucleic acid substrates. In particular, we show that the PARP14 macrodomain 1 is an active ADP-ribosyl hydrolase. We also demonstrate hydrolytic activity for the first macrodomain of PARP9. We reveal that expression of a PARP14 mutant with the inactivated macrodomain 1 results in a marked increase in... (More)

PARP14 is a mono-ADP-ribosyl transferase involved in the control of immunity, transcription, and DNA replication stress management. However, little is known about the ADP-ribosylation activity of PARP14, including its substrate specificity or how PARP14-dependent ADP-ribosylation is reversed. We show that PARP14 is a dual-function enzyme with both ADP-ribosyl transferase and hydrolase activity acting on both protein and nucleic acid substrates. In particular, we show that the PARP14 macrodomain 1 is an active ADP-ribosyl hydrolase. We also demonstrate hydrolytic activity for the first macrodomain of PARP9. We reveal that expression of a PARP14 mutant with the inactivated macrodomain 1 results in a marked increase in mono(ADP-ribosyl)ation of proteins in human cells, including PARP14 itself and antiviral PARP13, and displays specific cellular phenotypes. Moreover, we demonstrate that the closely related hydrolytically active macrodomain of SARS2 Nsp3, Mac1, efficiently reverses PARP14 ADP-ribosylation in vitro and in cells, supporting the evolution of viral macrodomains to counteract PARP14-mediated antiviral response.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Transferases, Poly(ADP-ribose) Polymerase Inhibitors, COVID-19, Antiviral Agents, Hydrolases, Poly(ADP-ribose) Polymerases/genetics
in
Science Advances
volume
9
issue
37
pages
18 pages
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • scopus:85171240255
  • pmid:37703374
ISSN
2375-2548
DOI
10.1126/sciadv.adi2687
language
English
LU publication?
yes
id
9c32dc5a-b44f-40c9-95a9-4b01da4ffeee
date added to LUP
2023-09-28 11:35:26
date last changed
2024-04-19 01:47:04
@article{9c32dc5a-b44f-40c9-95a9-4b01da4ffeee,
  abstract     = {{<p>PARP14 is a mono-ADP-ribosyl transferase involved in the control of immunity, transcription, and DNA replication stress management. However, little is known about the ADP-ribosylation activity of PARP14, including its substrate specificity or how PARP14-dependent ADP-ribosylation is reversed. We show that PARP14 is a dual-function enzyme with both ADP-ribosyl transferase and hydrolase activity acting on both protein and nucleic acid substrates. In particular, we show that the PARP14 macrodomain 1 is an active ADP-ribosyl hydrolase. We also demonstrate hydrolytic activity for the first macrodomain of PARP9. We reveal that expression of a PARP14 mutant with the inactivated macrodomain 1 results in a marked increase in mono(ADP-ribosyl)ation of proteins in human cells, including PARP14 itself and antiviral PARP13, and displays specific cellular phenotypes. Moreover, we demonstrate that the closely related hydrolytically active macrodomain of SARS2 Nsp3, Mac1, efficiently reverses PARP14 ADP-ribosylation in vitro and in cells, supporting the evolution of viral macrodomains to counteract PARP14-mediated antiviral response.</p>}},
  author       = {{Đukić, Nina and Strømland, Øyvind and Elsborg, Jonas Damgaard and Munnur, Deeksha and Zhu, Kang and Schuller, Marion and Chatrin, Chatrin and Kar, Pulak and Duma, Lena and Suyari, Osamu and Rack, Johannes Gregor Matthias and Baretić, Domagoj and Crudgington, Dorian Richard Kenneth and Groslambert, Joséphine and Fowler, Gerissa and Wijngaarden, Sven and Prokhorova, Evgeniia and Rehwinkel, Jan and Schüler, Herwig and Filippov, Dmitri V and Sanyal, Sumana and Ahel, Dragana and Nielsen, Michael L and Smith, Rebecca and Ahel, Ivan}},
  issn         = {{2375-2548}},
  keywords     = {{Humans; Transferases; Poly(ADP-ribose) Polymerase Inhibitors; COVID-19; Antiviral Agents; Hydrolases; Poly(ADP-ribose) Polymerases/genetics}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{37}},
  publisher    = {{American Association for the Advancement of Science (AAAS)}},
  series       = {{Science Advances}},
  title        = {{PARP14 is a PARP with both ADP-ribosyl transferase and hydrolase activities}},
  url          = {{http://dx.doi.org/10.1126/sciadv.adi2687}},
  doi          = {{10.1126/sciadv.adi2687}},
  volume       = {{9}},
  year         = {{2023}},
}